Myocardial fiber orientation is oblique in the epicardium and undergoes a transition in direction through the left ventricular wall that spans approximately 100 degrees. Although fiber anatomy has been studied in detail for at least 300 years, the functional consequences of this intricate arrangement are not fully understood. Fibers are joined together in a connective tissue matrix, and each may be functionally tethered to near or distant neighbors. indeed, recent studies have suggested that tethering may allow myocardial shortening to occur both in the direction of the fibers and also perpendicular to them. This "cross-fiber" shortening could result in the ability of the heart wall to shorten in two directions and thicken extensively in the third, a potent mechanism for ejection of blood. Magnetic Resonance Imaging tissue tagging is a new imaging method which allows the nonsurgical placement of short-lived magnetic markers into myocardium, and thus permits the tracking of tissue through the cardiac cycle, and accurate measurement of local deformations in the entire left ventricle. In this proposal, tagging is used to characterize regional left ventricular normal and shear strains during systole. To define how the heart's architecture enables extensive thickening to occur in systole, we will first determine whether the layers of the heart wall are tethered to each by correlating the angle at which maximum shortening occurs to the histologic fiber angle, at multiple regions in the left ventricle. We will describe myocardial deformation in detail by measuring left ventricular strains with respect to the fiber angle of each layer. This will allow us to define the importance of crossfiber shortening for systolic thickening by determining whether they co-vary from region to region of the left ventricle. The effect of epicardial fibers on the deformation of the perpendicular endocardial fibers will be assessed by selectively destroying epicardial layers with liquid nitrogen, and measuring the consequences on endocardial strains. Our findings will have relevance to the study of disease states such as cardiomyopathy and ischemia, in which a disturbed interaction between fibers may affect thickening and result in ventricular dysfunction.